4-Aminophenol → 4-(2-Methyl-4-pyridinyloxy)aniline

HRID 729981Notes

Reaction equation

[NH2:1][C:2]1[CH:7]=[CH:6][C:5]([OH:8])=[CH:4][CH:3]=1.CC(C)([O-])C.[K+].Cl[C:16]1[CH:21]=[CH:20][N:19]=[C:18]([CH3:22])[CH:17]=1.O>CN(C)C(=O)C>[CH3:22][C:18]1[CH:17]=[C:16]([O:8][C:5]2[CH:6]=[CH:7][C:2]([NH2:1])=[CH:3][CH:4]=2)[CH:21]=[CH:20][N:19]=1

Participants

Conditions

Temperature: 9 °C

Procedure

4-aminophenol (44.9 g, 410 mmol) was added to the 1 L 3-neck flask and dissolved with N,N-dimethylacetamide (600 mL). The stirred mixture was then cooled to 9° C. and potassium t-butoxide (46.18 g, 410 mmol) was added portionwise; the solution turned green and solidified before potassium t-butoxide addition was completed. Stirring was reestablished and a solution containing the 4-chloro-2-picoline (50 g, 390 mmol) in N,N-dimethylacetamide (400 mL) was slowly added and the mixture was heated at 90° C. for 17 h. The mixture was then allowed to cool to 45° C., filtered and concentrated to near dryness in vacuo to leave brown residue. The residue was slowly added to vigorously stirred water (1 L) and the suspension was stirred for 1 hr. The solids were then collected by suction filtration and washed with small amount of isopropanol, ether and dried to afford {4-[(2-Methylpyridin-4-yl) oxy] phenyl} amine (49.9 g, 64%) as light tan solid. 1H NMR (DMSO-d6) δ 8.21 (d, 1H), 6.78 (d, 2H), 6.57-6.63 (m, 4H), 5.10 (s, 2H), 2.35 (s, 3H); MS ES 201 (M+H)+, calcd 201, RT=1.04 min.

Workup

additionwas slowly added
temperaturethe mixture was heated at 90° C. for 17 h
temperatureto cool to 45° C.
filtrationfiltered
concentrationconcentrated
customto leave brown residue
stirringthe suspension was stirred for 1 hr
filtrationThe solids were then collected by suction filtration
washwashed with small amount of isopropanol, ether
customdried

Sources & evidence

ORD record: ord-a84c85fc4f004017a96d7b51d0cc32fe
Source dataset: uspto-grants-2009_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07582646B2

Reaction notes

Loading…